An independent panel that advises the FDA on cancer drugs weighed drugs from Spectrum Pharmaceuticals and Oncopeptides, casting negative votes for both.
The first was Spectrum’s poziotinib, which was developed to treat advanced non-small cell lung cancer (NSCLC) characterized by HER2 exon 20 insertion mutations, a rare genetic signature that governs approximately 2% to 4% of NSCLC cases.
FDA staff safety concerns noted at the suggested dose of 16 mg dose. In a clinical trial, 57% of patients had a dose reduction and 85% of patients had grade 3 or grade 4 adverse reactions. They also noted that Boston-based Spectrum is seeking accelerated approval for this 16 mg once-daily dose. but the planned confirmatory study will be at 8 mg twice daily. Last Thursday the commission voted 9 to 4 that the benefits of therapy do not outweigh the risks. The FDA’s decision on the drug is expected by November 24.
After Spectrum, Oncopeptides went before the advisory committee regarding its multiple myeloma drug Pepaxto. The FDA granted Pepaxto accelerated approval last year, but months later beeped who noted that a clinical trial found an increased risk of death associated with the drug. After that, Oncopeptides stopped selling the drug in the US
FDA staff aimed at lead to a confirmatory trial for Pepaxto that did not meet the goal of progression-free survival, a measure of how long patients live without their cancer getting worse. The staff also added that overall survival was worse in the Pepaxto group. The results showed a higher overall number and percentage of deaths in the Pepaxto group than in the group given standard multiple myeloma treatment. Regulators in Europe reached different conclusions about the drug, its approval last month. It is sold there as Pepaxti. But the FDA’s advisory committee remained unconvinced by the company’s analysis and European approval. When asked whether the drug’s benefits outweighed the risks, the committee answered “no” by 14 to 2 votes.
The standard qualifier for any FDA advisory committee meeting is that the regulator is not required to comply with the committee’s vote, but usually does. If that’s the case for Spectrum and Pepaxto, the odds don’t look good for a favorable decision from the FDA.
Here’s an overview of other recent regulatory news.
— Ferring Pharmaceutical’s Experimental Gut Microbiome Therapy Wins FDA Advisory Committee Support, which voted 13 to 4 that the treatment data are sufficient to support its efficacy. Switzerland-based Ferring designed its therapy, RBX2660, to reduce the recurrence of C. difficile infection (CDI). The committee also voted 12 to 1 with one abstention on whether the data are sufficient to support the safety of Ferring therapy in those 18 years of age and older after antibiotic treatment for recurrent CDI.
— Children have been excluded from many clinical trials because of what the FDA now says is a “misconception that excluding them from research actually protects them.” That thinking is changing, and the FDA has draft guidance issued defining an ethical framework for the inclusion and protection of children in clinical trials. It’s the draft open for public comment for the next three months before the FDA finalizes the guidelines.
— FDA placed a partial clinical retention of basic research, testing Viaskin, peanut allergy patch in development by DBV Technologies. That study has not yet begun, but France-based DBV said the agency had requested adjustments to the statistical analysis of patch adhesion, among other changes. According to DBV, the FDA said these modifications were necessary for the study to support a future biologics license application.
— Eli Lilly cancer cure Retevmo received FDA approval for the treatment of advanced solid tumors characterized by RET gene fusion. Accelerated approval covers the treatment of cancers that have progressed after at least one prior treatment. Retevmo won its initial fast-track approval in 2020 for the treatment of three RET-driven cancers: non-small cell lung cancer (NSCLC), thyroid cancer, and medullary thyroid cancer. With the latest tumor agnostic approval, the 2020 accelerated approval in non-small cell lung cancer has been converted to traditional.
—Clinical trials of Merck’s HIV drug, which were halted by the FDA last year, can now resumebut at a lower dose. Merck also said it would no longer continue development of the HIV drug, islatravir, for HIV prevention. The FDA put multiple trials of the drug on full or partial hold after observing that some patients treated with islatravir developed lower levels of two types of immune cells.
— Larimar Therapeutics was also able to resolve a clinical hold. Last year, the regulator paused a dosing clinical trial evaluating the biotech’s treatment for Friedrich’s ataxia, a rare neuromuscular disorder, after deaths were reported in a monkey study. All of these deaths occurred in monkeys given the highest dose of drug.
The pick up of full clinical detention comes with the imposition of partial detention. The planned Phase 2 trial now has a requirement that the FDA review data from the lower 25 mg dose group before the study escalates to a higher dose in the second cohort. Larimar said it expects to begin that study in the fourth quarter of this year; data is expected in the second half of 2023.
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